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@article{182835,
        author = {Ms. Siddhi Hemant Khanolkar and Dr. Bhongiri Bhargav and Mr. Anmulwad Babu Yamnaji and Mr. Akash Shashimohan Tiwari and Miss. Aakanksha Anil Zadbuke and Miss. Sneha Annaso Shinde},
        title = {CHEMOKINE RECEPTORS (E.G., CCR5, CXCR4) AS THERAPEUTIC TARGETS IN CANCER METASTASIS AND HIV},
        journal = {International Journal of Innovative Research in Technology},
        year = {2025},
        volume = {12},
        number = {2},
        pages = {3509-3516},
        issn = {2349-6002},
        url = {https://ijirt.org/article?manuscript=182835},
        abstract = {Chemokine receptors, particularly C-C chemokine receptor type 5 (CCR5) and C-X-C chemokine receptor type 4 (CXCR4), have garnered significant attention due to their pivotal roles in both pathological and physiological processes. These receptors, which belong to the G-protein coupled receptor (GPCR) superfamily, are primarily known for their function in directing the migration and positioning of immune cells via chemokine gradients. However, their roles extend beyond immune surveillance and inflammation; they are also hijacked in various disease states, notably cancer and viral infections such as human immunodeficiency virus (HIV).
In the context of HIV infection, CCR5 and CXCR4 serve as critical co-receptors facilitating viral entry into host CD4+ T cells. The virus initially uses CCR5 in early stages of infection (R5-tropic strains) and often shifts to CXCR4 usage (X4-tropic strains) as the disease progresses, contributing to immune system decline. This mechanism has led to the development of CCR5 antagonists like maraviroc, which blocks HIV entry and is approved for clinical use in HIV therapy. Similarly, in cancer biology, the aberrant expression of CCR5 and CXCR4 has been associated with tumor progression, angiogenesis, immune evasion, and particularly metastasis. CXCR4, in particular, interacts with its ligand CXCL12 (SDF-1) to promote cancer cell homing to distant metastatic niches such as bone marrow, liver, and lungs. This has positioned plerixafor (a CXCR4 antagonist initially used in stem cell mobilization) as a promising candidate in anticancer strategies. CCR5 overexpression has also been implicated in the aggressiveness of several cancers, including breast, prostate, and colorectal cancers. This review delves into the molecular and cellular mechanisms by which CCR5 and CXCR4 contribute to both HIV pathogenesis and cancer metastasis. We explore their downstream signaling cascades, cross-talk with other cellular pathways, and roles in the tumor microenvironment and immune modulation. Furthermore, we discuss current pharmacological modulators, including small molecule inhibitors, monoclonal antibodies, and gene-editing strategies targeting these receptors.Despite significant advances, challenges remain in the therapeutic exploitation of these targets. Issues such as drug resistance, receptor redundancy, and off-target effects complicate treatment efficacy. Moreover, the dualistic nature of these receptors—as both immune regulators and disease facilitators—requires nuanced approaches to ensure therapeutic success without impairing normal immune function.},
        keywords = {},
        month = {July},
        }